Autosomal dominant polycystic kidney disease (
ADPKD) is the most common congenital kidney disorder, generally caused by mutations in the PKD1 and PKD2 genes, coding for
polycystins 1 and 2. Its pathogenesis is accompanied by alterations of the cAMP, mTOR, MAPK/ERK, and JAK/STAT pathways.
ADPKD is clinically characterized by the formation of many growing
cysts with kidney enlargement and a progressive damage to the parenchyma, up to its complete loss of function, and the onset of
end-stage renal disease (
ESRD). The current aim of
ADPKD therapy is the inhibition of
cyst development and retardation of
chronic kidney disease progression. Several drugs have been recently included as potential
therapies for
ADPKD including
metformin, the
drug of choice for the treatment of
type 2 diabetes mellitus, according to its potential inhibitory effects on cystogenesis. In this review, we summarize preclinical and clinical evidence endorsing or rejecting
metformin administration in
ADPKD evolution and pathological mechanisms. We explored the biology of APDKD and the role of
metformin in slowing down cystogenesis searching PubMed and Clinical Trials to identify relevant data from the database inception to December 2020. From our research analysis, evidence for
metformin as emerging cure for
ADPKD mainly arise from preclinical studies. In fact, clinical studies are still scanty and stronger evidence is awaited. Its effects are likely mediated by inhibition of the ERK pathway and increase of AMPK levels, which are both linked to
ADPKD pathogenesis.